1. Field of the Invention
The present invention relates to a method of determining whether a liquid amount and/or quality of a contained liquid reagent are/is normal or not in a liquid-reagent-containing microchip, which is useful as μ-TAS (Micro Total Analysis System) or the like used for biochemical tests of DNA, protein, cell, immunity, blood, or the like, chemical synthesis, environmental analysis, and the like. In addition, the present invention relates to a liquid-reagent-containing microchip having a structure in which such determination can be made.
2. Description of the Background Art
A microchip having a hydraulic circuit inside has a small size, for example, of several cm square and several mm thickness. As compared with a series of experimental operations that have been performed in laboratories, the microchip has many advantages in that only a small amount of a sample and a reagent is required, cost is low, reaction speed is high, a test can be conducted with high throughput, and a test result can immediately be obtained at a site where the sample is taken. The microchip is suitably used, for example, for biochemical tests such as blood test.
Normally, a microchip contains a liquid reagent for treating a sample (such as blood) to be tested and/or analyzed or for mixing and reaction with a sample in advance in a chamber called a reagent holding portion in a hydraulic circuit, and the microchip normally contains and holds two or more types of liquid reagents in accordance with test items, in different reagent holding portions, respectively.
Normally, the microchip is required to be used for blood test or the like even after approximately six months to two years. An amount of the liquid reagent stored in the liquid-reagent-containing microchip is normally approximately from 1 to 100 μL. In order to hold such a very small amount of liquid reagent in the microchip for a long time, the microchip should be packed and sealed with a package material with high gas-barrier characteristics. Even though the microchip is sealed with a package material with high gas-barrier characteristics, possibility of decrease in the liquid reagent that has been contained in the microchip, for example, due to creation of a pin hole caused by damage of the package material during shipping or storage, cannot be denied.
In addition, if a resin such as PET (polyethylene teraphthalate) is used as a material for a substrate of the microchip, the liquid reagent that has been stored in the microchip gradually decreases due to water absorption and moisture absorption by the material for the substrate.
Accordingly, in particular when the liquid-reagent-containing microchip storing the liquid reagent in an amount as small as 1 to 100 μL for a long time is used, it is desirably guaranteed at the time of use that a necessary amount of liquid reagent has been stored in the microchip. Without such guarantee, for example, reliability of results of a test such as biochemical test is damaged.
For example, U.S. Pat. No. 5,590,052 describes a method of checking a liquid amount or the like of a contained liquid reagent at the time of use of a microchip and a microchip having a structure in which such a liquid amount or the like can be checked. More specifically, the publication describes a microchip including a chamber for checking a liquid amount or the like (hereinafter also referred to as an error checking portion). In addition, Japanese Patent Laying-Open No. 4-329362 describes an automatic analysis device including a comparison and determination portion determining whether a liquid amount is in a normal liquid amount state for quantification of a reagent component. The method of checking the liquid amount or the like described in these publications is directed to a method of checking a liquid reagent to be used for each type of the reagent, and in order to check a liquid amount or the like of a plurality of types of liquid reagents, checking should be carried out a plurality of times that correspond to the number of types of the liquid reagents. For example, if ten types of liquid reagents are contained in a single microchip, checking should be carried out ten times and ten error checking portions are necessary in the microchip.
Consequently, problems such as increase in a microchip area, a complicated test system, a larger size of a device, increase in the cost for the device, and increase in a test time for error checking arise.